COMMENTARY

Age at Menopause and Cognition: Timing Matters

JoAnn E. Manson, MD, DrPH

Disclosures

June 22, 2018

Hello. This is Dr JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women's Hospital in Boston, Massachusetts.

I'd like to talk with you about a recent report in the journal Neurology[1] about age at menopause and cognitive function during mid- and later life. This is an analysis from a British birth cohort study that included about 1300 women who had repeated cognitive assessments throughout life, including during childhood, but also at least four standardized assessments between the ages of 43 and 69.

The authors found that women who were older at the time of menopause had better cognitive function, particularly verbal memory. This was true whether the menopause was natural or surgical. But it was only with natural menopause that the associations persisted after adjustment for multiple confounding factors, including cigarette smoking, body mass index, hormone therapy use, education, socioeconomic status, and even cognitive abilities in early life.

The fact that the associations persisted for natural but not surgical menopause suggests that long-term—even lifelong—reproductive factors and hormonal exposures are influencing this relationship with cognition, and not just the short-term changes during the menopause transition.

Why would there be this association? We know from previous research that earlier age at menopause is linked to increased risk for several health conditions, including heart disease, osteoporosis, and diabetes, and other studies have also suggested cognitive decline.[2,3,4,5]

Regardless of the basis or etiology of this association, it appears that an early age at menopause is a marker of increased risk for cardiovascular disease and cognitive decline. This suggests that we should pay attention to a woman's age at menopause and be particularly vigilant about managing cardiovascular risk factors and even paying attention to primary prevention, such as encouraging regular physical activity and a heart-healthy diet to prevent cognitive decline. For example, the Mediterranean dietary pattern has been linked to a slowing of cognitive decline.[6]

A big gap in knowledge is the role of hormone therapy. Even randomized trials looking at women in early menopause and the effects of hormone therapy in preventing cognitive decline have shown inconsistent or generally neutral results. But these studies didn't focus on women with early menopause. The KEEPS trial is going to be looking at cognitive function an average of 8 years after an intervention in early menopause with hormone therapy, and it will include repeat cognitive testing as well as brain MRI and PET imaging of amyloid. Those results should be of interest. Overall, the findings of this study in neurology are very interesting and important, and useful to clinicians.

Thank you so much for your attention. This is JoAnn Manson.

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